Project Summary Inappropriate antibiotic use is a major public health problem and federal policy will soon require that all healthcare facilities adopt antibiotic stewardship programs (ASPs). As yet, there is no clear understanding of how to best implement effective stewardship programs. We propose to conduct a mixed-methods study with tightly linked qualitative and quantitative methods to address this gap in knowledge. Our study is designed to tackle fundamental questions about stewardship implementation, examining the degree to which organizational climate, steward self-efficacy, and provider autonomy influence implementation. Stewardship strategies in a large sample of hospitals will be characterized using the constructs and domains defined by the Consolidated Framework for Implementation Research (CFIR). We will perform this study in two large integrated healthcare systems, Veterans Health Administration (VHA) and Intermountain Healthcare, both of which report antibiotic use data to the National Healthcare Safety Network (NHSN) of the CDC. The NHSN antibiotic use module analyzes and benchmarks usage and reports back to participating facilities. First, antibiotic stewards will be interviewed by phone to explore organization climate and culture as well as other CFIR constructs. Information about each facility's stewardship resources and existing activities will also be collected. From these interviews and surveys, we will perform a cluster analysis to support construction of typology of hospital ASP strategies. The correlation between typology and antibiotic use will then be examined using joint statistical models to account for redistribution of drug classes. Pairs of sites within the same typology that have the highest discrepancies in antibiotic use will be chosen for on-site qualitative assessments. Through interviews and focus groups, we will develop narratives to address how contextual climate, the perceptions, training, motivation and self-efficacy of the steward, and the support and engagement of administration and providers affect ASP implementation and success across a range of healthcare inpatient facilities. Finally, we will examine the relationship between antibiotic use and antibiotic resistance outcomes using rigorous analytical models. Our comprehensive study of stewardship implementation will provide a roadmap for other hospitals seeking to implement an antibiotic stewardship program.